Drug Interaction:
Drug interactions - summary-
+ Sapropterin
Levodopa - exacerbation of convulsion or irritabilty during coadministration noticed.
Observe caution
Methotrexate- use caution while adminstering drug known to affect folate metabolism
( eg methotrexate). These drugs can reduce BH4 levels by inhibiting enzyme dihyropteridine
reductase.
PDE5 inhibitors eg sildenafil , vardenafil ) + Sapropeterin / Sapropepterin + PDE5 Inhibitors-
use caution when admninstring saproterin with drugs that affect nitric oxide mediated vasorelaxtion
eg sildenafil, tadalafil , vardenafil because both saperopterin and PDE5 inhibitors may induce
vasorelaxation and reduce blood pressure.
Indication:
Hyperphenylaninemia
Adverse Reaction:
Adverse reaction-
Dermatologic - contusion 5% rash 5%
GI - abdominal pain 5% diarrhea 8% vomiting 8%
Respiratory - cough 7% nasal congestion 4% pharyngolarygeal pain 10%
rhinorhea 11% upper respiratory ract infection 12%
Miscellaneous- headache 15% pyrexia 7%
Contra-Indications:
Special Precautions-
Blood Phe levels - heralth care providers knowledgable in the management of phenylketonuria
should direct treatment with sapropterin.
Prolonged elevation in blood Phe levels in patients with phenylketonuria can result in severe
neurological damage including severe mental retardation, microcephaly, delayed speech
and behavioural abnormalites.
Active management of dietary Phe intake while taking sapropterin is required to ensure adequate
Phe control and nutrional balance.
Non-responders to treatment- not all patients with phenylketonuria respond to treatment with
sepropterin. Response to treatment cannot be predetermined by laboratory testing
(eg. genetic testing) and can only be determined by a therapeutical trial of sapropterin.
Phe restricted diet- patients with phenylketonuria who are being treated with sapropterin
should be treated with Phe -restricted diet, The initiation of sapropterin therapy by trained
professionals to ensure that blood Phe control is maintained and the context of ongoing
dietary management
Hypersensitivity reactions- patients who have a known allergy to any of the components of
sapropterin should not take this medicine. Consider the risks and benefits of continued
treatment with saproterin in patients with mild to moderate allergic reactions eg. rash
Renal function impairment- patients with renal function impairment have not been evaluated in
clinical trials. Carefully monitor patients who have renal function impairment when they receive
sapropterin
Hepatic function impairment- carefully monitor who have hepatic function impairment when they
are receiving sapropterin because hepatic damage has been associated with impaired
Phe metabolism.
Pregnancy- women who are exposed to sapropterin during pregnancy are encouraged to
enroll in the sapropterin registry.
There are no adequate and well -controlled studies of sapropterin in pregnancy.
Good dietary control of Phe levesl during pregnancy is essential in reducing the incidence
of Phe -induced teratogenic effects.
Lactation- decide whether to discontinue breast feeding or the drug taking into account the
importance of th drug to the mother.
Children- Children with phenylketonuria , 4 to 16 years have been treated with sapropterin
in clinical studies. Safety and efficacy in children below 4 years have not been assessed.
Frequent blood sugar monitoring is recommended in children to ensure adequate blood
Phe level control.
Monitoring- carefully monitor patients with renal and/or hepatic function impairment.
Frequent blood monitoring is recommended in children to ensure adequate blood
Phe level control.
Monitor patients closely to ensure that blood Phe levels are not too low, if necessary
adjust dose of sapropterin
Dosages/ Overdosage Etc:
Indication-
Hyperphenalaninemia
Dosage-
Sapropterin tablets should be administered orally food to increase absorption , prefeably at the
same time each day.
The tablets should be dissolved in 4 to 80z ( 120 to 240 ml ) of water or apple juice and taken
within 15 minutes of dissolution
Patient Information:
1. Inform patients being treated with sapropterin to have frequent blood Phe measurements
and nutrional counseling with their health care providers, to ensure maintenance of Phe
levels at the desired range.
2. Advice patients that changes in dietary Phe intake can obscure the effect of sapropterin
on blood levels, and because not all patients will respond to treatment with sapriopterin.
3. Take baseline Phe measurements just prior to initiation of sapropterin response test.
4. Advice patients to actively manage their dietary Phe intake using medical foods and
natural resources of protein to ensure blood Phe control and adequate nutrional balance.
5. Advice patients that prolonged high blood Phe levels are neurotoxic and lead to impairment
of intelligence and other brain functions ( such as attentiveness )
Pharmacology/ Pharmacokinetics:
Pharmacology-
Sapropterin is a synthetic form of BH4 , the cofactor for the enzyme phenylamine reaction of
hydrolyase PAH. PAH hydroxylates Phe through an oxidative reaction to form tyrosine
Interaction with Food:
Sapropterin tablets should be administered orally food to increase absorption , prefeably at the
same time each day.
The tablets should be dissolved in 4 to 80z ( 120 to 240 ml ) of water or apple juice and taken
within 15 minutes of dissolution
Pregnancy and lactation:
Pregnancy-
Women who are exposed to sapropterin during pregnancy are encouraged to
enroll in the sapropterin registry.
There are no adequate and well -controlled studies of sapropterin in pregnancy.
Good dietary control of Phe levesl during pregnancy is essential in reducing the incidence
of Phe -induced teratogenic effects.
Lactation-
Decide whether to discontinue breast feeding or the drug taking into account the
importance of th drug to the mother.
Children-
Children with phenylketonuria , 4 to 16 years have been treated with sapropterin
in clinical studies. Safety and efficacy in children below 4 years have not been assessed.
Frequent blood sugar monitoring is recommended in children to ensure adequate blood
Phe level control.
Manufacturer Details